1. Field of the Invention
The present invention is directed, generally, to methods and materials for pain management and, more particularly, to methods and materials for pain management by increasing the antinociceptive effect of opioids.
2. Description of the Related Art
Chronic pain is a common complaint of patients who undergo surgical procedures or suffer from long term illness, including cancer, nerve injury, arthritis, or heart disease. Pharmacological agents used for treating chronic pain are often unsatisfactory because of the side effects accompanied the treatment. For example, opiates, at high doses, are apt to produce sedation, respiratory depression and tolerance, which severely limit their use. Recently, genetic approaches have been attempted to manage the chronic pain. One strategy is to increase the production of endogenous μ-opioid receptor ligands by introducing opioid precursor genes for enkephalin and β-endorphin into DRG neurons or meninges surrounding the spinal cord through adeno- or herpes viral vectors. The enhancement of opioid peptides effectively reduces nociceptive behaviors in rats. So far the success of this approach has been limited by several including transient expression of the target genes and potential possibilities of tolerance development as result of upregulation of opioids.
Furthermore, while there are many studies addressing the δ-opioid receptors (DOR) expression following nerve injury, the findings are quite conflicting. Differences in d-opioid receptor agonists or antibodies used in the studies contribute to the confusing results. The most recent and relevant finding is the study of Kabli and Cahill (1) who show that following sciatic nerve ligation, δ-opioid receptor expression increases on both ipsi- and contralateral side of the ligation. In addition, morphine is effective for 14 days and the d-opioid receptor agonist, deltorphin, is effective for 21 days in reducing allodynic responses in injured rats. The study cannot explain why morphine and deltorphin are rather ineffective in reducing allodynia responses in nerve-injured rats when compared with normal rats. More importantly, Kali and Cahill's finding did not suggest any benefit would be derived by an increase in δ-opioid receptor expression in dorsal root ganglions. Thus, there remains a need to more effectively manage chronic pain by increasing the antinociceptive effect of opioids. The present invention fulfills this long-standing need in the art by increasing levels of opioid receptors in neurons by the administration of nucleic acid constructs.